Myxedema Coma or Crisis: Practice Essentials, Background, Pathophysiology

Myxedema is a term generally used to denote severe hypothyroidism. Myxedema coma, occasionally called myxedema crisis, is a rare, life-threatening clinical condition that consists of severe hypothyroidism with decompensation. The disorder most often occurs in patients with long-standing, undiagnosed hypothyroidism and is typically precipitated by a systemic illness. Patients with myxedema coma are usually severely ill, with significant hypothermia and depressed mental status. ^{[1, 2]}

Myxedema coma is a medical emergency that must be attended to right away. If the diagnosis is suspected, immediate management is necessary before confirming the diagnosis due to the high associated mortality rate. Patients with myxedema coma should be treated in an intensive care unit (ICU) with continuous cardiac monitoring. Initial steps in therapy include supportive measures, thyroid hormone replacement, and glucocorticoid therapy (until adrenal insufficiency is excluded).

Signs and symptoms

The following features may be present:

• Hypothermia

• Hypotension

• Decreased pulse pressure, normal systolic pressure, elevated diastolic pressure, slow pulse

• Periorbital edema, swelling of the face and lips, thickened nose, enlarged tongue (macroglossia), enlarged tonsils, coarse or thin hair

• The thyroid is generally small or nonpalpable; however, it can be enlarged

• Slow respiratory rate, hypoventilation, congestion, pleural effusion

• Soft or distant heart sounds, diminished apical impulse, bradycardia, enlarged heart, pericardial effusion

• Abdominal distention due to ileus or ascites; diminished or absent bowel sounds

• Urinary bladder distention

• Cold extremities

• Non-pitting edema of the hands and feet

• Cool, pale, dry, scaly, and thickened skin; ecchymoses; purpura

• Dry, brittle nails

• Confusion, stupor, obtundation, or coma; slow speech; seizures; reflexes with a slow relaxation phase

Workup

Laboratory studies include the following:

• Thyroid-stimulating hormone (TSH) and free thyroxine (T4) levels

• Serum electrolytes and serum osmolality - Hyponatremia with low serum osmolality is common

• Serum creatinine - Usually elevated

• Serum glucose - Hypoglycemia is common, but this may also suggest concomitant adrenal insufficiency

• Complete blood count (CBC) - Leukocytosis is not common; bands and/or a left shift may be the only signs of infection

• Arterial blood gases - Increased partial pressure of CO2 (PCO2) and decreased partial pressure of oxygen (PO2) are usually found

• Cultures for sepsis - Blood cultures and others (such as urine and sputum) as indicated

Imaging studies include chest radiographs, computed tomography (CT) scans of the brain, and other studies, as dictated by the patient’s condition.

Electrocardiographic findings may include the following:

• Sinus bradycardia

• Variable degrees of heart block

• Low-amplitude QRS complexes

• Nonspecific ST-segment changes

• Flattened or inverted T waves

• Prolonged QT intervals

• Ventricular arrhythmias

Management

Thyroid therapy

Because of the rarity of myxedema coma, randomized trials comparing different treatment modalities are not available. There is no agreement on the type of thyroid hormone preparation to prescribe (levothyroxine [T4] alone, liothyronine [T3] alone, or T4 and T3 combined), or on the dose, frequency, and route of administration.

Because gastrointestinal absorption may be compromised, IV thyroid therapy is initially advised. T3 has a quicker onset of action and greater biologic activity than T4. In addition, the conversion of T4 to T3 is usually impaired in hypothyroidism and in the setting of severe systemic illness.

We suggest the administration of both T4 and T3 in the treatment of myxedema coma.

Glucocorticoid therapy

Patients with myxedema coma can have concomitant primary adrenal insufficiency, while patients with secondary hypothyroidism may have associated secondary adrenal insufficiency. Glucocorticoids should be administered until the possibility of adrenal insufficiency is excluded.

Myxedema is a clinical state of severe thyroid hormone deficiency that results in the failure of multiple organs. ^{[3, 4, 5, 6]}  The term myxedema is also used to describe the dermatologic changes that occur in hypothyroidism and occasionally in hyperthyroidism; myxedema refers specifically, in these cases, to the dermal deposition of mucopolysaccharides, which causes the affected area to swell. When skin changes occur in hyperthyroidism, most commonly Graves disease, the disorder is called pretibial myxedema.  

Myxedema coma typically occurs in patients with long-lasting, previously undiagnosed hypothyroidism and is generally precipitated by infection, congestive heart failure, acute myocardial infarction, cerebrovascular accident, gastrointestinal bleeding, or medications. ^{[7, 8, 9, 10, 11, 12]}

Myxedema coma occurs because of long-standing, undiagnosed or undertreated hypothyroidism. Although any of the causes of hypothyroidism can lead to myxedema coma, the most common is chronic autoimmune thyroiditis. It can also occur in patients who had a thyroidectomy or who underwent radioactive iodine therapy for hyperthyroidism. Rare causes of myxedema coma include secondary hypothyroidism and medications such as lithium and amiodarone.

Given the importance of thyroid hormones in cell metabolism, long-standing hypothyroidism is associated with a reduced metabolic rate and decreased oxygen consumption, affecting all body systems. ^[13]  Consequently, myxedema coma can also result when a hypothyroidism-induced decrease in drug metabolism leads to overdosing of medications, including sedatives, hypnotics, and anesthetic agents.

United States

Hypothyroidism is one of the most common endocrine disorders, affecting 11.7% of the US population. ^[14]  However, myxedema coma is rare (with the precise prevalence unknown), likely due to the common availability thyroid function testing and, therefore, the widespread early detection of hypothyroidism.

International

In areas where there is an adequate intake of iodine, the most common cause of hypothyroidism is autoimmune thyroid disease, with a prevalence that varies from 5.6% to 11.4%. ^[15]  In regions where inadequate amounts of iodine are ingested, the most common cause of hypothyroidism is iodine deficiency. Severe hypothyroidism is observed only with severe iodine deficiency, which is generally found in isolated, mountainous regions of South America, Africa, and Asia. An observational study showed that the estimated incidence of myxedema coma in Japan was 1.08 per million people per year. ^[16]

Myxedema coma is a medical emergency. If the condition is not promptly diagnosed and treated, the mortality rate can be as high as 50%. Even with immediate recognition and appropriate medical intervention, mortality rates of up to 25% have been observed. ^{[17, 18, 19]}

Factors associated with poor prognosis are body temperature less than 93°F (33.9°C), persistent hypothermia unresponsive to 72 hours of therapy, advanced age, bradycardia (< 44 beats per minute), sepsis, myocardial infarction, and hypotension. In addition, the patient's level of consciousness and scores on the Glasgow Coma Scale and the Acute Physiology and Chronic Health Evaluation (APACHE) II have been found to be most predictive of survival. ^{[19, 20]}

Patients who are diagnosed with hypothyroidism should be counseled regarding the necessity of taking daily thyroid hormone replacement and monitoring of thyroid tests on a regular basis.

Patients with a history of thyroiditis or who have undergone thyroid irradiation or thyroid surgery should be counseled that hypothyroidism might occur in the future. They should be educated about the symptoms of hypothyroidism and should understand the importance of seeking timely medical advice for examination and testing.